Genetic testing in focal segmental glomerulosclerosis: in whom and when?

Background: Genetic causes are increasingly recognized in patients with focal segmental glomerulosclerosis (FSGS), but it remains unclear which patients should undergo genetic study. Our objective was to determine the frequency and distribution of genetic variants in steroid-resistant nephrotic syndrome FSGS (SRNS-FSGS) and in FSGS of undetermined cause (FSGS-UC). Methods: We performed targeted exome sequencing of 84 genes associated with glomerulopathy in patients with adult-onset SRNS-FSGS or FSGS-UC after ruling out secondary causes. Results: Seventy-six patients met the study criteria; 24 presented with SRNS-FSGS and 52 with FSGS-UC. We detected FSGS-related disease-causing variants in 27/76 patients (35.5%). There were no differences between genetic and non-genetic causes in age, proteinuria, glomerular filtration rate, serum albumin, body mass index, hypertension, diabetes or family history. Hematuria was more prevalent among patients with genetic causes. We found 19 pathogenic variants in COL4A3-5 genes in 16 (29.3%) patients. NPHS2 mutations were identified in 6 (16.2%) patients. The remaining cases had variants affecting INF2, OCRL, ACTN4 genes or APOL1 high-risk alleles. FSGS-related genetic variants were more common in SRNS-FSGS than in FSGS-UC (41.7% vs 32.7%). Four SRNS-FSGS patients presented with NPHS2 disease-causing variants. COL4A variants were the most prevalent finding in FSGS-UC patients, with 12 patients carrying disease-causing variants in these genes. Conclusions: FSGS-related variants were detected in a substantial number of patients with SRNS-FSGS or FSGS-UC, regardless of age of onset of disease or the patient's family history. In our experience, genetic testing should be performed in routine clinical practice for the diagnosis of this group of patients.

Effect of balance Solution on the Peritoneal Membrane in Automated Peritoneal Dialysis.

Interference of conventional peritoneal dialysis fluids (cPDFs) with peritoneal membrane cell functions may be attributed to the dialysis fluid's low pH, high glucose concentration, and/or the presence of glucose degradation products (GDPs), the last of which leads to higher levels of advanced glycation end-products (AGEs). It has been suggested that the peritoneal membrane might be better preserved by using biocompatible solutions, including cancer antigetn 125 (CA125). This prospective, open-label, multicentre, randomized, controlled, cross-over phase IV study compared the in vivo biocompatibility of a neutral-pH, low-GDP peritoneal dialysis (PD) solution (balance) with a cPDF in automated PD (APD) patients. Our study revealed a significantly increased appearance rate and concentration of CA125 in the peritoneal effluent of APD patients treated with the neutral-pH, low-GDP solution balance versus a conventional PD solution.

Kidney injury after sodium phosphate solution beyond the acute renal failure / Daño renal después de preparación colónica con soluciones de fosfato. Más allá del fracaso renal agudo

Antecedentes y objetivos: La colonoscopia con polipectomía con fines de cribado reduce la incidencia del cáncer colorrectal y la mortalidad por esta enfermedad. Una preparación colónica aceptable es una de las claves para conseguir mejores resultados con esta técnica. Las soluciones de fosfato de sodio oral (OSP) fueron muy utilizadas en la década de los noventa del siglo pasado. Su eficacia era similar a la de las soluciones de polietilenglicol (PEG), pero más baratas y con una administración sencilla. Se han descrito series de casos de pacientes con insuficiencia renal aguda provocada por OSP. Sin embargo, en cohortes amplias de pacientes no se observó ninguna diferencia en la incidencia de daño renal entre estas dos soluciones. Métodos: Entre 2006 y 2009 identificamos 12 casos de nefropatía por fosfato tras preparación con OSP para colonoscopia. Se realizó el seguimiento de todos los pacientes durante 6 meses. Todos los pacientes habían recibido una única dosis. Resultados: Analizamos 12 casos de nefropatía por fosfato; 3 se manifestaron con IRA y 9 presentaron daño renal crónico. Cuatro de los casos se confirmaron mediante biopsia renal. Un paciente con IRA precisó hemodiálisis en el momento del diagnóstico, sin que experimentara recuperación posterior. Dos pacientes (ambos con daño crónico) recuperaron totalmente su función renal anterior. Los demás pacientes (9) presentaron una pérdida media en la filtración glomerular estimada de 24ml/min/1,73m2. Conclusiones: El uso de OSP puede ocasionar daño renal tanto agudo como crónico. Sin embargo, el daño crónico fue el más frecuente. Ambas formas de presentación suponen una pérdida considerable e irreversible de función renal. Nuevos estudios que analicen el daño renal secundario a preparación colónica deben considerar estos dos patrones distintos de daño (AU)

Background and objectives: Screening colonoscopy with polipectomy reduces colonorectal cancer incidence and mortality. An adequate bowel cleansing is one of the keys to achieving best results with this technique. Oral sodium phosphate solution (OSP) had a widespread use in the 90s decade. Its efficacy was similar to polyethylene glycol (PEG) solution, but with less cost and convenient administration. Series of patients with acute renal failure due to OSP use have been reported. However, large cohorts of patients found no difference in the incidence of renal damage between these two solutions. Methods: From 2006 to 2009 we identified twelve cases of phosphate nephropathy after colonoscopy prepared with OSP. All patients were followed up to six months. All patients had received just a single dose. Results: We analyzed 12 cases with phosphate nephropathy; three patients debuted with AKI and nine patients had chronic renal injury. Four cases were confirmed with renal biopsy. One patient with AKI needed hemodialysis at diagnosis without subsequent recovery. Two patients (both with chronic damage) fully recovered their previous renal function. The remaining patients (nine) had an average loss of estimated glomerular filtration rate of 24ml/min/1.73m2. Conclusions: The use of OSP can lead to both acute and chronic renal damage. However, chronic injury was the most common pattern. Both forms of presentation imply a significant and irreversible loss of renal function. Further studies analyzing renal damage secondary to bowel cleaning should consider these two different patterns of injury (AU)

Kidney injury after sodium phosphate solution beyond the acute renal failure.

BACKGROUND AND OBJECTIVES: Screening colonoscopy with polipectomy reduces colonorectal cancer incidence and mortality. An adequate bowel cleansing is one of the keys to achieving best results with this technique. Oral sodium phosphate solution (OSP) had a widespread use in the 90s decade. Its efficacy was similar to polyethylene glycol (PEG) solution, but with less cost and convenient administration. Series of patients with acute renal failure due to OSP use have been reported. However, large cohorts of patients found no difference in the incidence of renal damage between these two solutions. METHODS: From 2006 to 2009 we identified twelve cases of phosphate nephropathy after colonoscopy prepared with OSP. All patients were followed up to six months. All patients had received just a single dose. RESULTS: We analyzed 12 cases with phosphate nephropathy; three patients debuted with AKI and nine patients had chronic renal injury. Four cases were confirmed with renal biopsy. One patient with AKI needed hemodialysis at diagnosis without subsequent recovery. Two patients (both with chronic damage) fully recovered their previous renal function. The remaining patients (nine) had an average loss of estimated glomerular filtration rate of 24ml/min/1.73m(2). CONCLUSIONS: The use of OSP can lead to both acute and chronic renal damage. However, chronic injury was the most common pattern. Both forms of presentation imply a significant and irreversible loss of renal function. Further studies analyzing renal damage secondary to bowel cleaning should consider these two different patterns of injury.

Peritoneal Dialysis Can Be an Option for Dominant Polycystic Kidney Disease: an Observational Study.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) has been considered a relative contraindication for peritoneal dialysis (PD), although there are few specific studies available. METHODS: A multicenter historical prospective matched-cohort study was conducted to describe the outcome of ADPKD patients who have chosen PD. All ADPKD patients starting PD (n = 106) between January 2003 and December 2010 and a control group (2 consecutive patients without ADPKD) were studied. Mortality, PD-technique failure, peritonitis, abdominal wall leaks and cyst infections were compared. RESULTS: Patients with ADPKD had similar age but less comorbidity at PD inclusion: Charlson comorbidity index (CCI) 4.3 (standard deviation [SD] 1.6) vs 5.3 (SD 2.5) p < 0.001, diabetes mellitus 5.7% vs 29.2%, p < 0.001 and previous cardiovascular events 10.4% vs 27.8%, p < 0.001. No differences were observed in clinical events that required transient transfer to hemodialysis, nor in peritoneal leakage episodes or delivered dialysis dose. The cyst infection rate was low (0.09 episodes per patient-year) and cyst infections were not associated to peritonitis episodes. Overall technique survival was similar in both groups. Permanent transfer to hemodialysis because of surgery or peritoneal leakage was more frequent in ADPKD. More ADPKD patients were included in the transplant waiting list (69.8 vs 58%, p = 0.04) but mean time to transplantation was similar (2.08 [1.69 - 2.47] years). The mortality rate was lower (2.5 vs 7.6 deaths/100 patient-year, p = 0.02) and the median patient survival was longer in ADPKD patients (6.04 [5.39 - 6.69] vs 5.57 [4.95 - 6.18] years, p = 0.024). CONCLUSION: Peritoneal dialysis is a suitable renal replacement therapy option for ADPKD patients.

First episodes of peritoneal infection: description and prognostic factors.

INTRODUCTION: Peritonitis is one of the most common and severe complications associated with peritoneal dialysis (PD), constituting the primary cause of catheter loss and exit from the dialysis technique. The incidence and aetiology of peritonitis episodes vary based on geographical region, and change over time. For this reason, it is vital to maintain an updated understanding of the current risk factors and prognostic factors associated with peritonitis. METHOD: We performed an observational, multi-centre, prospective cohort study with a maximum follow-up period of 7 years (2003-2010), which included 1177 patients and a total of 476 first episodes of peritonitis (total: 1091 cases of peritonitis). RESULTS: We describe the characteristics of the first episode of peritonitis from a large and current study sample. The factors associated with a shorter interval until the first episode of peritonitis as selected by the multivariate analysis included prior cardiovascular comorbidity (Hazard Ratio [HR]: 1.25 [1.04-1.58]), having previously received haemodialysis (HR: 1.39 [1.10-1.76]) or a kidney transplant (HR: 1.38 [1.10-1.93]), having started PD on a manual modality (HR: 1.39 [1.13-1.73]), and initial age >70 years (HR: 1.53 [1.23-1.90]). The first episode of peritonitis was associated with a 7.8% rate of recurrence, an 11.7% rate of catheter removal, and a mortality rate within one month of the episode of 1.3%. The progression of peritonitis infections depended on the type of causal microorganism. We calculated a greater risk for gram-negative bacterial infections (Odds Ratio [OR]: 5.31 [2.26-12.48]) and the aggregate group of infections caused by multiple microorganisms, fungal infections, and mycobacterial infections (OR: 38.24 [13.84-105.63]), as compared to gram-positive bacterial infections. CONCLUSION: The development of a first case of peritonitis depends on the characteristics of the patient upon starting dialysis, comorbidities present, and the technique used. Patients at a greater risk for peritonitis must receive special care during training and follow-up.

Effect of dual blockade of the renin-angiotensin system on the progression of type 2 diabetic nephropathy: a randomized trial.

BACKGROUND: Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers has been shown to lessen the rate of decrease in glomerular filtration rate in patients with diabetic nephropathy. STUDY DESIGN: A multicenter open-label randomized controlled trial to compare the efficacy of combining the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor blocker irbesartan with that of each drug in monotherapy (at both high and equipotent doses) in slowing the progression of type 2 diabetic nephropathy. SETTING & POPULATION: 133 patients with type 2 diabetic nephropathy (age, 66 ± 8 years; 76% men) from 17 centers in Spain. INTERVENTION: Patients were randomly assigned (1:1:2) to lisinopril (n = 35), irbesartan (n = 28), or the combination of both (n = 70). OUTCOMES: The primary composite outcome was a >50% increase in baseline serum creatinine level, end-stage renal disease, or death. RESULTS: Baseline values for mean estimated glomerular filtration rate and blood pressure were 49 ± 21 mL/min/1.73 m(2) and 153 ± 19/81 ± 11 mm Hg. Mean geometric baseline proteinuria was protein excretion of 1.32 (95% CI, 1.10-1.62) g/g creatinine. After a median follow-up of 32 months, 21 (30%) patients in the combination group, 10 (29%) in the lisinopril group, and 8 (29%) in the irbesartan group reached the primary outcome. HRs were 0.96 (95% CI, 0.44-2.05; P = 0.9) and 0.90 (95% CI, 0.39-2.02; P = 0.8) for the combination versus the lisinopril and irbesartan groups, respectively. There were no significant differences in proteinuria reduction or blood pressure control between groups. The number of adverse events, including hyperkalemia, was similar in all 3 groups. LIMITATIONS: The study was not double blind. The sample size studied was small. CONCLUSIONS: We were unable to show a benefit of the combination of lisinopril and irbesartan compared to either agent alone at optimal high doses on the risk of progression of type 2 diabetic nephropathy.

Tratamiento quirúrgico de las estenosis yuxtaanastomóticas en las fístulas arteriovenosas radiocefálicas de hemodiálisis. Nueva anastomosis proximal / Surgical treatment of juxta-anastomotic stenosis in radiocephalic fistula. A new proximal radiocephalic anastomosis

Introducción: Las estenosis yuxtaanastomóticas son la causa más frecuente de disfunción en las fístulas radiocefálicas (FAV RC) para hemodiálisis. Estas estenosis provocan bajo flujo de la fístula con mala calidad de la diálisis y pueden evolucionar a la trombosis del acceso. El tratamiento de estas lesiones puede ser radiológico o quirúrgico; la elección de uno u otro es tema de discusión. En nuestro centro se utilizó por consenso el tratamiento quirúrgico de forma sistemática. Método: Hemos realizado un estudio prospectivo desde 1998 hasta 2009. Se incluyeron todas las FAV RC con disfunción o trombosis secundaria a una estenosis yuxtaanastomótica. El diagnóstico se realizó mediante fistulografía, salvo en los casos de trombosis, en los que fue clínico. El tratamiento en todos los casos fue quirúrgico, realizándose una nueva anastomosis radiocefálica proximal a la estenosis (RC PROX). Se analizó la permeabilidad (primaria y secundaria) tanto para las FAV RC iniciales como para las RC PROX (..) (AU)

Introduction: The juxta-anastomotic stenosis is the most frequent cause of dysfunction in radiocephalic fistulas for haemodialysis. This adversity can cause low flow or thrombosis. The appropriate treatment of these lesions is under debate. Method: A prospective study was performed from 1998 to 2009. All dysfunctional radiocephalic fistulas due to juxta-anastomotic stenosis were included (n=96). The diagnosis was made by fistulografy in low flow cases and clinical evidence in cases of thrombosis. The repair was performed using a new proximal radiocephalic anastomosis in all cases. Patency following surgical intervention was estimated with the Kaplan-Meier method. Results: A total of 96 proximal radiocephalic anastomoses were performed during the study period. Mean surveillance time was 57.27 months (95% CI: 47.53-67.02). Sixty-six patients were male, and the mean age was 67 years. Scheduled surgery was performed in 70.5% of cases and 29.5% were emergency procedures, 92% of which were ambulatory. Technical success was achieved in 100% without any complications. Mean primary patency at 1, 2, 3, 4, and 5 years was 89.4%, 75%, 70.4%, 65%, and 56%, respectively. Additional procedures (n=16) were required in 14 cases (twelve new proximal anastomoses and four cases of arteriovenous graft placement), resulting in mean secondary patency at 1, 2, 3, 4, and 5 years of 93.7%, 92.1%, 89.6%, 87%, and 82.6%, respectively. Mean secondary patency of initial dysfunctional radiocephalic fistulas at 1, 2, 3, 4, and 5 years was 95%, 95%, 93.2%, 89.1%, and 86.6%, respectively. Conclusions: In our experience the proximal radiocephalic anastomosis can significantly extend fistula functionality in patients with juxta-anastomotic stenosis (AU)

Surgical treatment of juxta-anastomotic stenosis in radiocephalic fistula. A new proximal radiocephalic anastomosis.

INTRODUCTION: The juxta-anastomotic stenosis is the most frequent cause of dysfunction in radiocephalic fistulas for haemodialysis. This adversity can cause low flow or thrombosis. The appropriate treatment of these lesions is under debate. METHOD: A prospective study was performed from 1998 to 2009. All dysfunctional radiocephalic fistulas due to juxta-anastomotic stenosis were included (n=96). The diagnosis was made by fistulografy in low flow cases and clinical evidence in cases of thrombosis. The repair was performed using a new proximal radiocephalic anastomosis in all cases. Patency following surgical intervention was estimated with the Kaplan-Meier method. RESULTS: A total of 96 proximal radiocephalic anastomoses were performed during the study period. Mean surveillance time was 57.27 months (95% CI: 47.53-67.02). Sixty-six patients were male, and the mean age was 67 years. Scheduled surgery was performed in 70.5% of cases and 29.5% were emergency procedures, 92% of which were ambulatory. Technical success was achieved in 100% without any complications. Mean primary patency at 1, 2, 3, 4, and 5 years was 89.4%, 75%, 70.4%, 65%, and 56%, respectively. Additional procedures (n=16) were required in 14 cases (twelve new proximal anastomoses and four cases of arteriovenous graft placement), resulting in mean secondary patency at 1, 2, 3, 4, and 5 years of 93.7%, 92.1%, 89.6%, 87%, and 82.6%, respectively. Mean secondary patency of initial dysfunctional radiocephalic fistulas at 1, 2, 3, 4, and 5 years was 95%, 95%, 93.2%, 89.1%, and 86.6%, respectively. CONCLUSIONS: In our experience the proximal radiocephalic anastomosis can significantly extend fistula functionality in patients with juxta-anastomotic stenosis.

Anemia development and cardiovascular risk management in nonanemic stage 3 chronic kidney disease.

BACKGROUND/AIM: There is little information on the development of anemia in the early stages of chronic kidney disease. The aim of this study was to analyze the onset of renal anemia in a cohort of initially nonanemic chronic kidney disease patients followed up in nephrology clinics. METHODS: This epidemiological, prospective, three-year, multicenter study enrolled patients aged 18-78 years with stage 3 chronic kidney disease without anemia. Interim analysis was performed on the data collected during the first 12 months. RESULTS: The study included 432 patients, average age 63.6 years (range 22-78 years, 70% male). The main etiologies of chronic kidney disease were glomerular (11.6%), interstitial (10.4%), vascular (29.4%), and diabetic (16.9%). The percentages of patients with comorbidities were 33.8% diabetes (2.5% type 1), 69% dyslipidemia, and 93% hypertension. During the first year, 12.4% of patients developed anemia. The chronic kidney disease progression rate was low: proteinuria was 0.46 +/- 0.8 g/24 h at one year versus 0.67 +/- 1.0 g/24 h at baseline. Diabetic patients showed a greater prevalence of previous cardiovascular events (50.0% vs. 24.5%) and worse control of some modifiable cardiovascular risk factors: smoking (13.4% vs. 8.6%), obesity (BMI > 30 kg/m(2), 33.6% vs. 25.3%), target blood pressure (<130/80 mmHg, 21.0% vs. 27.9%), and proteinuria (0.8 +/- 1.1 vs. 0.6 +/- 0.9 g/day). CONCLUSIONS: After one year, 12.4% of patients developed anemia. Diabetic patients had a higher cardiovascular risk and limited blood pressure control. The overall control of cardiovascular risk was unsatisfactory.

[Definition of processes and indicators for the management of vascular accesses for hemodialysis]. / Definición de procesos e indicadores para la gestión de accesos vasculares para hemodiálisis.

INTRODUCTION: The prevalence of renal replacement therapy has increased, affecting 885 patients per million inhabitants. More than 50% of these patients require hemodialysis with permanent vascular access. In our center a multidisciplinary group was organized to manage processes related to vascular access for hemodialysis. OBJECTIVES: To define processes for the management of vascular access for hemodialysis and to evaluate these processes. MATERIAL AND METHOD: Setting. Level III hospital in the autonomous community of Madrid serving 485,000 inhabitants. STUDY PERIOD: 2002-2004. METHODOLOGY: A multidisciplinary working group was set up. The three most frequent processes were defined and described. Flow charts were used for graphical representation. Quality criteria and indicators were defined with prospective monitoring of electronic medical records, design of a specific surgical protocol, and retrospective analysis. RESULTS: Comparison of the results with the literature. First vascular access. The percentage of patients with arteriovenous fistulas on starting hemodialysis. Percentage of prevalent patients with venous access (autologous fistula, prosthetic device, catheter). Maintenance of access: Rate of thrombosis in autologous-prosthetic arteriovenous fistulas. Percentage of rescued arteriovenous fistulas after thrombosis. Rate of temporary catheters. Resource management. Percentage of ambulatory interventions. Rate of admissions related to arteriovenous fistulas. CONCLUSIONS: Arteriovenous fistulas are the main source of morbidity and hospital admission in patients with chronic renal failure in hemodialysis programs. Multidisciplinary management achieves results above the standards described in the literature. There do not appear to be other determining factors for these results, since the technical procedures performed do not differ from those described in the literature.

Definición de procesos e indicadores para la gestión de accesos vasculares para hemodiálisis / Definition of processes and indicators for the management of vascular accesses for hemodialysis

Introducción. La prevalencia del tratamiento renal sustitutivo ha aumentado hasta 885 pacientes por millón de habitantes. Más del 50% de estos pacientes necesitan hemodiálisis (HD) con acceso vascular (AVH) permanente. En nuestro centro se organizó un grupo multidisciplinar para gestionar los procesos relacionados con el AVH. Objetivos. Definición y evaluación de procesos para gestionar los AVH. Material y método. Ámbito: hospital de tercer nivel de la Comunidad de Madrid, referencia para 550.000 habitantes. Período de estudio: 2002-2004. Método: se constituyó un grupo de trabajo multidisplinario. Definición y descripción de los 3 procesos más frecuentes. Se utilizaron flujogramas para representación gráfica. Se definieron criterios e indicadores de calidad, con monitorización prospectiva en la historia clínica electrónica, diseño de protocolo quirúrgico específico y análisis retrospectivo. Resultados. Comparación de resultados con los de la literatura: Primer acceso vascular: porcentaje de pacientes con fístulas arteriovenosas (FAV) desarrollado al comenzar HD; porcentaje de pacientes prevalentes con AVH autólogo/protésico/ catéter. Mantenimiento del acceso: tasa de trombosis FAV autóloga-protésica, porcentaje de AVH rescatadas tras trombosis, tasa de catéteres temporales. Gestión de recursos: porcentaje de intervenciones ambulatorias, tasa de ingresos relacionados con AVH. Conclusiones. Los AVH son la fuente de morbilidad e ingresos hospitalarios principal de los pacientes con insuficiencia renal crónica en programas de HD. La gestión multidisciplinar ha permitido conseguir resultados por encima de los estándares descritos en la bibliografía. No parece que haya otros factores determinantes de estos resultados, ya que los procedimientos técnicos realizados no difieren de los descritos en la bibliografía (AU)

Introduction. The prevalence of renal replacement therapy has increased, affecting 885 patients per million inhabitants. More than 50% of these patients require hemodialysis with permanent vascular access. In our center a multidisciplinary group was organized to manage processes related to vascular access for hemodialysis. Objectives. To define processes for the management of vascular access for hemodialysis and to evaluate these processes. Material and method. Setting. Level III hospital in the autonomous community of Madrid serving 485,000 inhabitants. Study period: 2002-2004. Methodology: A multidisciplinary working group was set up. The three most frequent processes were defined and described. Flow charts were used for graphical representation. Quality criteria and indicators were defined with prospective monitoring of electronic medical records, design of a specific surgical protocol, and retrospective analysis. Results. Comparison of the results with the literature. First vascular access. The percentage of patients with arteriovenous fistulas on starting hemodialysis. Percentage of prevalent patients with venous access (autologous fistula, prosthetic device, catheter). Maintenance of access: Rate of thrombosis in autologous-prosthetic arteriovenous fistulas. Percentage of rescued arteriovenous fistulas after thrombosis. Rate of temporary catheters. Resource management. Percentage of ambulatory interventions. Rate of admissions related to arteriovenous fistulas. Conclusions. Arteriovenous fistulas are the main source of morbidity and hospital admission in patients with chronic renal failure in hemodialysis programs. Multidisciplinary management achieves results above the standards described in the literature. There do not appear to be other determining factors for these results, since the technical procedures performed do not differ from those described in the literature (AU)